Biodegradable Drug Delivery Composition

Abstract

The present disclosure provides a biodegradable drug delivery composition including a vehicle and an insoluble component comprising beneficial agent dispersed in the vehicle. Typically, the composition is not an emulsion, but has a low viscosity and further provides for minimized initial burst and sustained release of the beneficial agent over time. Also provided, are kits including the biodegradable drug delivery composition or components thereof, as well as methods of making and using the biodegradable drug delivery composition.

1 .- 22 . (canceled) 
     
     
         23 . A composition comprising:
 a vehicle comprising:
 sucrose acetate isobutyrate, 
 a biodegradable polymer present in an amount of from about 5% to about 40% by weight of the vehicle, the biodegradable polymer having a weight average molecular weight ranging from 2000 Daltons to 10,000 Daltons, and 
 a hydrophobic solvent present in an amount of from about 60% to about 95% by weight of the vehicle; and 
   a complex dispersed in the vehicle, the complex having a solubility of less than 1 mg/mL in the vehicle at 25° C.,   wherein the complex comprises:
 a protein, peptide, nucleic acid, or low molecular weight compound, the low molecular weight compound having a molecular weight of less than or equal to about 800 Daltons, and 
 a counterion of the protein, peptide, nucleic acid, or low molecular weight compound, 
   wherein the composition has a zero shear viscosity less than 1,200 centipoise at 25° C., and   wherein the composition is not an emulsion.   
     
     
         24 . The composition of  claim 23 , wherein the composition is not a gel. 
     
     
         25 . The composition of  claim 23 , wherein the composition has a G″/G′ ratio of greater than or equal to 10. 
     
     
         26 . The composition of  claim 23 , wherein the biodegradable polymer comprises at least one member selected from poly-lactide, poly-glycolide, poly-caprolactone, and copolymers and terpolymers thereof. 
     
     
         27 . The composition of  claim 23 , wherein the biodegradable polymer comprises at least one of polylactic acid and poly(lactic acid-co-glycolic acid). 
     
     
         28 . The composition of  claim 23 , wherein the hydrophobic solvent comprises at least one member selected from benzyl alcohol, methyl benzoate, ethyl benzoate, n-propyl benzoate, isopropyl benzoate, butyl benzoate, isobutyl benzoate, sec-butyl benzoate, tert-butyl benzoate, isoamyl benzoate, and benzyl benzoate. 
     
     
         29 . The composition of  claim 23 , wherein the hydrophobic solvent comprises benzyl benzoate. 
     
     
         30 . The composition of  claim 23 , wherein the vehicle further comprises benzyl alcohol. 
     
     
         31 . The composition of  claim 23 , wherein the vehicle further comprises ethanol. 
     
     
         32 . The composition of  claim 23 , wherein the counterion comprises a divalent metal, and wherein the complex further comprises one of a polymeric cationic complexing agent and a polymeric anionic complexing agent. 
     
     
         33 . The composition of  claim 23 , wherein the counterion comprises at least one member selected from protamine, poly-lysine, poly-arginine, polymyxin, carboxy-methyl-cellulose (CMC), poly-adenosine, and poly-thymine. 
     
     
         34 . The composition of  claim 23 , wherein the counterion comprises protamine. 
     
     
         35 . The composition of  claim 23 , wherein the counterion comprises a divalent metal or salt thereof. 
     
     
         36 . The composition of  claim 23 , wherein the counterion is selected from Zn 2+ , Mg 2+ , and Ca 2+ . 
     
     
         37 . The composition of  claim 36 , wherein the complex further comprises protamine. 
     
     
         38 . The composition of  claim 23 , wherein the counterion comprises protamine, wherein the molar ratio of the protein, peptide, nucleic acid, or low molecular weight compound and protamine is approximately 1:0.1 to 0.5. 
     
     
         39 . The composition of  claim 23 , wherein the counterion comprises zinc and protamine, wherein the molar ratio of the protein, peptide, nucleic acid, or low molecular weight compound, zinc, and protamine is approximately 1:0.4 to 2:0.1 to 0.5. 
     
     
         40 . The composition of  claim 23 , wherein the complex comprises the protein, peptide, or nucleic acid. 
     
     
         41 . A method of making a composition, comprising:
 combining a biodegradable polymer and a hydrophobic solvent to form a vehicle, wherein the biodegradable polymer is included in an amount of from about 5% to about 40% by weight of the vehicle, and the hydrophobic solvent is included in an amount of from about 95% to about 60% by weight of the vehicle; and   dispersing an insoluble beneficial agent complex in the vehicle, wherein the insoluble beneficial agent complex has a solubility of less than 1 mg/mL in the vehicle at 25° C., thereby providing a composition having a zero shear viscosity less than 1,200 centipoise at 25° C., which composition is not an emulsion.   
     
     
         42 . A method of administering a beneficial agent to a subject, comprising:
 administering to the subject via injection a composition comprising
 a single-phase vehicle comprising a biodegradable polymer present in an amount of from about 5% to about 40% by weight of the vehicle, and a hydrophobic solvent present in an amount of from about 95% to about 60% by weight of the vehicle; and 
 an insoluble beneficial agent complex dispersed in the vehicle, wherein the composition has a zero shear viscosity less than 1,200 centipoise at 25° C. and is not an emulsion.